OBJECTIVETo investigate the difference in the efficacy between clonidine transdermal patch and haloperidol tablets in the treatment of moderate to severe tic disorders in children.

METHODSA total of 134 children with moderate to severe tic disorders were randomly divided into clonidine group (n=70) and haloperidol group (n=64). The clonidine and haloperidol groups were treated with clonidine transdermal patch and haloperidol tablets respectively, and the treatment lasted for 8 weeks in both groups. The Yale Global Tic Severity Scale (YGTSS) was used to evaluate the conditions of the children before and after treatment, and the adverse events during the treatment were recorded.

RESULTSThe haloperidol group had a significantly better treatment outcome than the clonidine group after one week of treatment (P<0.05); the treatment outcome showed no significant difference between the two groups after 3, 5, and 8 weeks of treatment (P>0.05). The clonidine group had significantly less reductions in the motor tics, vocal tics, and function impairment scores and total score of YGTSS than the haloperidol group after one week of treatment (P<0.05); there were no significant differences in YGTSS score reductions between the two groups after 3, 5, and 8 weeks of treatment (P>0.05). The clonidine group had a significantly lower overall incidence of adverse events than the haloperidol group (8% vs 37%; P<0.01).

CONCLUSIONSClonidine transdermal patch and haloperidol are both effective in the treatment of moderate to severe tic disorders in children. The clonidine transdermal patch, despite slow action, has comparable efficacy and fewer adverse effects compared with haloperidol.

Child ; Child, Preschool ; Clonidine ; administration & dosage ; Female ; Haloperidol ; therapeutic use ; Humans ; Male ; Severity of Illness Index ; Tic Disorders ; drug therapy ; Transdermal Patch

BACKGROUND/AIMS: DA-9701 is a novel prokinetic agent. In the present study, we investigated the effect of DA-9701 on the motility of the gastric antrum in the normal and clonidine-induced hypomotility in an in vivo animal model. METHODS: A strain gauge force transducer was sutured on the gastric antrum to measure the contractile activity in rats. A total of 28 rats were subclassified into the 4 groups: (1) the placebo group, (2) the DA-9701 group, (3) the placebo group in the clonidine-pretreated rats, and (4) the DA-9701 group in the clonidine-pretreated rats. After the basal recording, either placebo (3% [w/v] hydroxypropylmethyl cellulose) or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. In the clonidine-pretreated rats, either placebo or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. RESULTS: Oral administration of DA-9701 did not significantly alter the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the placebo group. The administration of clonidine decreased the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the administration of placebo. This reduction of the antral motility by the administration of clonidine was not observed in the clonidine-pretreated DA-9701 group. The percentage of the motility index in the postprandial period was significantly greater in the clonidine-pretreated DA-9701 group, compared with the clonidine-pretreated placebo group. CONCLUSIONS: DA-9701 improves the hypomotility of the gastric antrum induced by clonidine, suggesting its gastroprokinetic effect in the pathologic condition.
Administration, Oral ; Animals ; Clonidine ; Meals ; Models, Animal ; Postprandial Period ; Pyloric Antrum* ; Rats* ; Transducers

INTRODUCTIONClonidine is used with local anaesthetics to improve analgesia. However, the improvement conferred when clonidine is used together with ropivacaine is controversial. Thus, the present study aimed to evaluate the improvement in analgesia when clonidine is used together with ropivacaine for supraclavicular brachial plexus block.

METHODSThis was a prospective, randomised, double-blind controlled study. A total of 75 patients who were scheduled to undergo supraclavicular block were randomly assigned into three groups (i.e. clonidine, lignocaine and control groups) of 25. Patients in all three groups received 20 mL of 0.75% ropivacaine. In addition to that, patients in the clonidine group received 1 mL of clonidine (150 μg) plus 9 mL of saline, patients in the lignocaine group received 10 mL of 2% lignocaine with adrenaline (1:200,000), and patients in the control group received 10 mL of saline. The characteristics of anaesthesia and analgesia for these three groups were assessed.

RESULTSThe addition of 2% lignocaine with adrenaline to ropivacaine led to earlier onset of the sensory block (by 4.88 mins), but no increase in the duration of analgesia when compared to analgesia using ropivacaine alone. The addition of clonidine to ropivacaine led to earlier onset of sensory and motor blocks (by 2.88 mins and 3.28 mins, respectively), as well as an increased duration of sensory and motor blocks (by 222.64 mins and 192.92 mins, respectively) when compared to analgesia using ropivacaine alone. The total duration of analgesia was increased by 208.24 mins with clonidine when compared to analgesia using ropivacaine alone. There were no significant differences in sedation score and no side effects in all three groups.

CONCLUSIONWhen compared to the use of ropivacaine alone, the addition of 150 μg clonidine to ropivacaine for brachial plexus block achieved earlier analgesic onset and improved duration of analgesia, without unwanted side effects.

Adult ; Amides ; administration & dosage ; Analgesia ; methods ; Anesthesia ; methods ; Anesthetics ; administration & dosage ; Anesthetics, Local ; administration & dosage ; Antihypertensive Agents ; administration & dosage ; Brachial Plexus Block ; methods ; Clonidine ; administration & dosage ; Double-Blind Method ; Drug Therapy, Combination ; methods ; Female ; Humans ; Lidocaine ; administration & dosage ; Male ; Middle Aged ; Prospective Studies

PURPOSE: To screen for diabetic autonomic neuropathy of the pupil using 0.5% apraclonidine and 0.1% pilocarpine and to evaluate the early diagnostic value of this pharmacologic pupillary test by assessing the relationship between pupillary and cardiovascular autonomic neuropathies. METHODS: A total of 22 diabetic patients were recruited. Baseline pupillary diameter (PD) and the difference in PD between the test eye and the control eye before and after instillation of apraclonidine and pilocarpine were measured. All patients also underwent cardiovascular autonomic function (CAF) testing. RESULTS: Baseline PD in room light correlated with duration of diabetes mellitus (DM, p=0.049) and the presence of DM retinopathy (DMR, p=0.022). Eleven patients (50%) had positive apraclonidine tests, and two patients had positive pilocarpine tests. The patients who had positive pilocarpine tests also had positive apraclonidine tests. Patients who had a positive pupillary test had a significantly higher rate of positive CAF tests (p=0.032). CONCLUSIONS: Pupillary autonomic neuropathy was related to the duration of diabetes and the degree of DMR. There was also a significant correlation between pupillary autonomic neuropathy and cardiovascular autonomic neuropathy (CAN). Also, sympathetic nerve dysfunction occurred prior to parasympathetic dysfunction in this study. A simple pharmacologic pupillary test can help manage complications in diabetic patients because patients with pupillary autonomic dysfunction have an increased risk of CAN.
Adrenergic alpha-Agonists/administration & dosage/diagnostic use ; Adult ; Aged ; Clonidine/administration & dosage/*analogs & derivatives/diagnostic use ; Diabetic Nephropathies/*diagnosis/physiopathology ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Miosis/*chemically induced/physiopathology ; Miotics/administration & dosage/diagnostic use ; Ophthalmic Solutions ; Pilocarpine/administration & dosage/*diagnostic use ; Pupil/drug effects/*physiology ; Reproducibility of Results

OBJECTIVEChildren with Tourette's syndrome (TS) have a poor treatment compliance due to side effects and inconvenient administration of oral drugs. This study explored the efficacy and safety of clonidine transdermal patch for treating TS in children.

METHODSA total of 119 children with TS were randomly treated with the clonidine transdermal patch (n=65) or with oral haloperidol (n=54). The therapeutic efficacy was assessed based on the results of the Yale Global Tic Severity Scale (YGTSS) 4 weeks after treatment.

RESULTSThe clonidine transdermal patch group showed a higher reduction in the overall tic symptom scores (61.5+/-7.5%) than that in the haloperidol group (41.0+/-6.3%; p<0.05). Clonidine transdermal patch treatment was effective in 53 patients (81.5%) and 36 patients (67.5%) showed effective to oral haloperidol (p>0.05). Mild side effects (decrease of blood pressure and dizziness) were observed in 1 patient in the clonidine transdermal patch group. Mild hypermyotonia, drowsiness or lassitude as side effects occurred in 6 patients in the haloperidol group.

CONCLUSIONSClonidine transdermal patch is effective for the treatment of TS in children and its side effects are mild and rare.

Administration, Cutaneous ; Adolescent ; Child ; Child, Preschool ; Clonidine ; administration & dosage ; adverse effects ; pharmacology ; Female ; Haloperidol ; therapeutic use ; Humans ; Male ; Tourette Syndrome ; drug therapy

OBJECTIVETo investigate the effects of intrathecal escin and clonidine, used alone or in combination, in the treatment of neuropathic pain in rats and the possible mechanism.

METHODSNinety-six male SD rats weighing 250-300 g were chronically implanted with lumbar intrathecal catheters. One week later, the left L5 and L6 spinal nerve roots were ligated to establish the model of spinal nerve ligation neuropathic pain (SNL). The rats were then randomly divided into 16 groups (n=6), including the control (saline), escin, clonidine, escin+clonidine, and the antagonist groups. Mechanical withdrawal threshold was assessed before and at 5, 10, 20, 30, 40, 50 and 60 min after intrathecal administration was evaluated. The maximal possible effect (MPE) was calculated and the effect of the treatments on the neuropathic pain. Isobolographic analysis was performed to characterize any potential interactions between the drugs.

RESULTSMPE was significantly higher in escin group (20, 40 microg), clonidine group (2, 5, 10 microg) and escin+clonidine group [1/4, 1/2 (escin ED(50)+clonidine ED(50))] than in the saline group (P<0.05). Intrathecal escin (5-40 microg) or clonidine (1-10 microg) alone dose-dependently alleviated neuropathic pain. Isobolographic analysis suggested a synergistic effect between escin and clonidine. Intrathecal pretreatment with yohimbine (20 microg) antagonized the effects of clonidine (P<0.01) and attenuated the action of the combination treatment with escin and clonidine (P<0.05).

CONCLUSIONIntrathecal escin and clonidine alone can dose-dependently relieve neuropathic pain. Escin and clonidine produce a synergistic effect for pain relief, which may involve the actions of alpha(2) receptor and Ca(2+) channel.

Analgesics ; administration & dosage ; Animals ; Clonidine ; administration & dosage ; Drug Synergism ; Escin ; administration & dosage ; Injections, Spinal ; Male ; Pain ; drug therapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spinal Nerve Roots ; injuries

OBJECTIVETo investigate the effects of intrathecal ouabain and tizanidine injection for treatment of neuropathic pain in rats.

METHODSMale SD rats weighing 250-300 g were randomly divided into 5 groups (n = 6), namely the control group, ouabain group, tizanidine group, combined ouabain and tizanidine injection group, and the antagonist group. Intrathecal catheter was implanted 7 days before spinal nerve ligation to establish the neuropathic pain model. Mechanical withdrawal threshold (MWT) before and after intrathecal administration of the agents was recorded in the rats. Isobolographic analysis was performed to evaluate the interactions between the agents.

RESULTSIntrathecal injection of ouabain (0.25-5 microg) or tizanidine (0.5-5 microg) alone produced dose-dependent analgesic effect against the neuropathic pain (P < 0.05). Isobolographic analysis revealed a synergistic interaction between ouabain and tizanidine. Intrathecal pretreatment with atropine (5 microg) or yohimbine (20 microg) antagonized the effects of ouabain and tizanidine administered alone or in combination (P < 0.05).

CONCLUSIONIntathecal injection of ouabain or tizanidine produces dose-dependent analgesic effects against neuropathic pain, and their synergistic effect after combined injection probably involves the cholinergic transmission and alpha2 receptor.

Analgesics ; administration & dosage ; Animals ; Clonidine ; administration & dosage ; analogs & derivatives ; Injections, Spinal ; Ouabain ; administration & dosage ; Pain ; drug therapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spinal Nerves ; injuries

Administration, Cutaneous ; Adolescent ; Antihypertensive Agents ; administration & dosage ; therapeutic use ; Child ; Clonidine ; administration & dosage ; therapeutic use ; Double-Blind Method ; Female ; Humans ; Male ; Tic Disorders ; drug therapy

OBJECTIVE: To observe the effect of intrathecal injection of ketamine and clonidine for chronic constriction injury (CCI) in rats. METHODS: Thirty-two SD male rats weighing 220-280 g were anesthetized with intraperitoneal chloral hydrate 300 mg/kg. A catheter was implanted in the subarachnoid space at the lumbal region and CCI rat models were made successfully. On the 4th day after the surgery, the rats were randomly divided into 4 group: a control group,injecting 0.9%NS 20 microL intrathecally; a ketamine group, injecting ketamine 1 mg/kg(20 microL) intrathecally; a clonidine group (CL), injecting clonidine 20 microg/kg (20 microL) intrathecally; a combined ketamine and clonidine group, injecting ketamine 0.5mg/kg and clonidine 10 g/kg (20 microL) intrathecally, once a day for 1 week. BME-410A Plantar Analgesia Tester was used to measured pain threshold before the administration and 30 min after the administration. The rats were killed after the test was finished. And then we detected the nitric oxide synthase (NOS) activity and the NO production in the spinal cord. RESULTS: The combined injection of ketamine (0.5mg/kg)and clonidine(10 g/kg) produced significantly more potent analgesia than the injection of ketamine (1 mg/ kg) or clonidine (20 microg/ kg)alone. The NOS activity and the production of NO in the combined injection group were significantly lower than those of the single injection group (P<0.05). The weight of rats post-administration increased obviously in the 4 groups (P<0.05). CONCLUSION The combined injection of ketamine and clonidine can produce synergistic ab-irritation without obvious side effects.
Analgesics ; administration & dosage ; adverse effects ; therapeutic use ; Animals ; Clonidine ; administration & dosage ; adverse effects ; therapeutic use ; Drug Combinations ; Injections, Spinal ; Ketamine ; administration & dosage ; adverse effects ; therapeutic use ; Male ; Neuralgia ; drug therapy ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; drug effects ; metabolism

AIMTo determine clonidine in rabbit plasma by LC-MS.

METHODSThe LC-MS system consisted of Waters Alliance 2790 HPLC and Micromass ZQ-4000 MS. The HPLC was performed by using XTerra C18 (150 mm x 2.1 mm ID, 5 microm). The mobile phase, consisting of acetonitrile/ammonium hydrogen carbonate solution, was maintained to a flow-rate of 0.2 mL x min(-1) and the linear gradient elution was adopted. Mass spectrum was obtained by using electrospray ionization interface and the m/z of SIM was 230.

RESULTSThe average recovery was high and the method was reproducible. The calibration curve showed good linearity in the range of 1 - 80 microg x L(-1), the lowest limit of detection was 0.05 microg x L(-1). The Cmax, AUC0-t, and Tmax value of the pharmacokinetics parameter were (27 +/- 9) microg x L(-1), (5,352 +/- 1,121) microg x L(-1), (79 +/- 17) h.

CONCLUSIONThe results demonstrated that the method had high sensitivity, good selectivity, accuracy and precision. It is used to determine the clonidine concentration in plasma. The transdermal patch can deliver clonidine to the surface of rabbit skin stably for periods of up to 1 week after a single application.

Administration, Cutaneous ; Animals ; Antihypertensive Agents ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Chromatography, High Pressure Liquid ; methods ; Clonidine ; administration & dosage ; blood ; pharmacokinetics ; Rabbits ; Spectrometry, Mass, Electrospray Ionization ; methods